Modification of endocrine active potential by mixtures
K. Gaido, L. You, and S. Safe
CIIT Centers for Health Research, 6 Davis Drive, Research
Triangle Park,
NC 27709, USA; Department of Veterinary Physiology and Pharmacology,
Texas A&M University, College Station, TX 77843, USA
Abstract:
Wildlife and humans are exposed to a complex mixture of endocrine
active chemicals. The activity of a specific chemical in any mixture
can be modified through interactions with other components of the mixture.
The toxic equivalency factor (TEF) approach for risk assessment was
developed for chemicals such as halogenated aromatics that induce their
effects through ligand-activated receptors. For persistent halogenated
aromatic AhR agonists, this approach has some utility. However, the
use of the TEF approach for endocrine active compounds is confounded
by the unique tissue- and response-specific activities of these structurally
diverse compounds. The term selective receptor modulator describes the
ability of a natural or synthetic receptor ligand to manifest agonist
activity in one tissue or for one response and antagonist activity in
other tissues or for another response in the same tissue. Thus, it is
possible for chemicals in a mixture to behave in an additive manner
for one response and an antagonist manner for another response. A mechanisms-based
hazard risk assessment of endocrine active chemical mixtures must account
for these multiple variables.
*Report from a SCOPE/IUPAC project: Implication of
Endocrine Active Substances for Human and Wildlife (J. Miyamoto and
J.Burger, editors). Other reports are published in this issue,
pp. 1617-2615.
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